This is a new, fast track application that explains the need for additional therapeutics for the treatment of chronic hepatitis B virus (HBV) infection. Discovery of novel non cytotoxic L-nucleosides with potent anti-HBV activity that, when used in combination, act synergistically is described. These L-nucleosides are reported to inhibit the viral DNA polymerase and replication without effect upon cellular polymerases or mitocohndrial function and have been shown to significantly reduce viral load in the chronic woodchuck hepatitis model. Funding from SBIR phase 1 and 2 will be used to select and develop the combination of the L-nucleosides with the greatest potential for commercialization. Phase 1 will determine pharmacology, toxicology and antiviral potency of two and three L nucleoside combinations in the woodchuck chronic hepatitis model. PROPOSED COMMERCIAL APPLICATION: Chronic treatment of Hepatitis B virus infection. Delay in progression to cirrhosis and hepatocellular carcinoma. Possible elimination of Hepatitis B virus.